The inventive compositions include antiplaque agents which are glyceroglycolipids containing at least one .beta.-D-galactose group having a structure shown below.
Natural glycolipids are known in the art and these structures have been elucidated. The term glycolipid refers to any of a class of lipids that, upon hydrolysis, yield a sugar (e.g., galactose or glucose), and a lipid (e.g. substituted glycerol group). One major class of these glycolipids belong to the glycero glycolipids, i.e., a glycolipid based around a glycerol frame structure. For example, the compound may have a sugar structure at one end of the glycerol structure instead of an--OH group and an ester linkage at one or both of the other --OH groups that would normally be found on glycerol. Another example of a glyceroglycolipid is a compound having a sugar structure at one end of a glycerol structure instead of an --OH group and ether linkage on one or both of the other --OH groups that would normally be found on glycerol.
Yet another example of a glyceroglycolipid might be a compound with a sugar group on one end of the glycerol structure instead of an --OH group and an amine group (i.e., NRR.sup.1) at one or both of the other --OH groups normally found in glycerol, and in particular amines wherein one or both of R and R.sup.1 are alkyl chains.
Concurrently filed commonly assigned applications Ser. No. 07/816,423 and Ser. No. 07/816,4 both now abandoned disclose the general utility of glyceroglycolipids having an amine and an ether linkage as surfactants in personal products and detergent formulations. Oral hygiene compositions according to the present invention may include surfactant molecules taught by the concurrently filed application, but the present invention is based, in part, on the discovery that glyceroglycolipids containing a .beta.-D-galactose group and having specific structures described in a greater detail below provide an antiplaque benefit by disrupting stereospecific bacterial binding.
It is generally recognized that the development of dental plaque begins with the adhesion of bacteria to the teeth. Bacterial adhesion to tooth surfaces usually involves stereospecific interactions between cell surface binding proteins, referred to as adhesins, and cognate structures which form binding sites either in salivary pellicle, or on the surfaces of other bacteria resident in plaque, or in the extracellular plaque matrix (Gibbons, R. J.; J Dent Res 68,750-760).
Many of the oral bacterial adhesins described in the art exhibit carbohydrate-specific binding and are often found on filamentous extensions (i.e., pili or fimbriae) which protrude from cell surfaces. These carbohydrate recognition structures, which are also referred to as lectins, mediate binding to host-derived or microbial-derived saccharide-containing structures on the teeth. Several different bacterial lectins have been described in the literature. By far, the lectins most commonly expressed by plaque bacteria are .beta.-galactoside-specific or "lactose sensitive" adhesins. The genera of bacteria which produce .beta.-galactoside-specific adhesins cover a diverse taxonomic range, including Actinomyces, Streptococcu, Porphyromonas, Fusobacterium, Haemophilus, Capnocytophaga, Veillonella, Prevotella, Staphylococcus, and Neisseria; these represent both primary and secondary colonizers of the teeth (Kollenbrander, P. E.; Crit Rev Microbiol 17:137-159). Kollenbrander notes that bacterial coaggregation plays an active role in formation of dental plaque on the teeth and adherence of bacteria to epithelial cells in the oral econiche.
Most attempts to control plaque through anti-adhesion mechanisms have involved non-stereospecific inhibition of bacterial attachment to the teeth, usually with compositions containing surface-active polymers. For instance, G.B. Pat. No. 2,224,204A and U.S. Pat. No. 4,877,603 disclose oral compositions which include phosphonate-containing polymers that inhibit bacterial attachment to hydroxyapatite surfaces. Similarly, U.S. Pat. No. 4,663,202 discloses a method for treating surfaces with combinations of polymers which form barriers that retard bacterial adsorption.
With respect to blocking stereospecific interactions which mediate oral bacterial adherence, the use of mono- and oligosaccharides has been described, as inhibitors of lectin-mediated adhesion to human cells. For instance, U.S. Pat. No. 5,071,977 describes oligosaccharides isolated from S. sanguis, which inhibit the build-up of adhesive dental plaque. Gaffar et al. (U.S. Pat. No. 5,002,759) disclose oligosaccharides containing either a galactose moiety (which may be .beta.-D-galactose and/or a fucose moiety as agents in dentifrice preparations for inhibiting adherence of Streptococcus pyogenes to human epithelial cells. European Patent Application 184,121 discloses the use of galactose and/or lactose as anti-caries agents in foods, drinks, and pharmaceutical preparations. Neeser (U.S. Pat. Nos. 4,992,420 and 4,994,441) describes kappa-caseino-glycopeptide compounds and desialylated derivatives thereof (the derivatives contain .beta.-D-galactose groups) as inhibitors of in vitro adhesion by dental plaque bacteria to human erythrocytes.
Lynch et al. (U.S. Pat. No. 4,855,128) disclose polysaccharides such as xanthan gum, gum tragacanth, guar gum, gum karaya, chondroitin sulfate, polygalacturonic acid (pectin), sodium alginate and carrageenans of the kappa/lambda configuration as plaque-inhibitory agents which inhibit bacterial coaggregation; carrageenans of kappa/lambda configuration and chondroitin sulfate contain .beta.-D-galactose.
Stromberg et al. (J. Biol. Chem. 265,11251-11258) disclose that N-acetyl-galactosamine-.beta.1,3-galactose-O-ethyl (a .beta.-galactosamine glycoside) is an inhibitor of binding by Actinomyces viscosus and Actinomyces naeslundii to human erythrocytes. McIntire et al. (Infection and Immunity, vol. 41, No. 2, 848-850) have described O-glycosides of galactose-.beta.1,3-N-acetyl-galactosamine, including phenyl, phenylethyl, and nitrophenyl derivatives, which inhibit coaggregation between Actinomyces sp. and Streptococcus sanguis; McIntire et al. note that the addition of aglycones increased the inhibitory activity significantly but not greatly.
Stromberg et al. ("Synthetic Receptoranalogues Prevent Plaque Formation in Man", Abstracts of International Association for Dental Research Scandinavian Division, Helsinki, Aug. 22-24 1991) disclose a study demonstrating the plaque inhibitory activity of GalNAc.beta.-3Gal.alpha.1-O-ethyl, which blocked adherence of Actinomyces strains 12104 and LY7. Clinical plaque strains were evaluated in a mouth rinse experiment including five human individuals. The study is said to demonstrate that receptor analogues such as GalNAc.beta.-3Gal.alpha.1-O-ethyl, may prove useful in future antiplaque therapy. However, glycosides made from disaccharides such as disaccharides disclosed by the Stromberg and McIntire references are expensive molecules to synthesise; hence, their practical utility is limited to the study of stereospecifity of bacterial binding.
Lectin binding site analogues derived from saccharides but distinct from the compounds employed in the present invention have been disclosed for applications in a non-dental environment. Mardh et al. (U.S. Pat. No. 4,851,338) disclose the use of glycosides of structure 1 (which may contain .beta.-D-galactose) for diagnosing the presence of Staphylococcus bacteria and bacteria from the genus Bordatella pertussis. ##STR1##
Wherein R.sub.1, R.sub.2, and R.sub.3 are same or different and are hydrogen or an organic residue, for example lower alkyl, lower acyl, or a carbohydrate residue or an inorganic residue, such as sulphate or phosphate, and wherein OR.sub.1 is an .alpha.- or .beta.- configuration.
Dental art heretofore has not made available a dentifrice composition containing relatively cost-effective synthetic glyceroglycolipid antiplaque agents which are capable of inhibiting bacterial adhesive interactions.
Accordingly, it is an object of the present invention to provide oral hygiene compositions which include glyceroglycolipids as antiplaque agents.
It is another object of the invention to provide methods of inhibiting bacterial adhesion in the oral cavity.
These and other objects of the invention will become more apparent from the detailed description and examples that follow.